Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 3833 | 11722;11723;11724 | chr2:178741736;178741735;178741734 | chr2:179606463;179606462;179606461 |
| N2AB | 3516 | 10771;10772;10773 | chr2:178741736;178741735;178741734 | chr2:179606463;179606462;179606461 |
| N2A | None | None | chr2:None | chr2:None |
| N2B | 3470 | 10633;10634;10635 | chr2:178741736;178741735;178741734 | chr2:179606463;179606462;179606461 |
| Novex-1 | 3595 | 11008;11009;11010 | chr2:178741736;178741735;178741734 | chr2:179606463;179606462;179606461 |
| Novex-2 | 3662 | 11209;11210;11211 | chr2:178741736;178741735;178741734 | chr2:179606463;179606462;179606461 |
| Novex-3 | None | None | chr2:None | chr2:None |
Information
Reported SAVs
| SNV | RS | DUET |
PolyPhen-2 |
Condel |
Rhapsody |
REVEL |
MVP |
Source |
MAF |
Disease |
Zygosity |
Site annotation |
mCSM PPI |
Predicted PPI site |
Comments |
AFR |
AMR |
AMS |
ASJ |
EAS |
EUR |
FIN |
MDE |
NFE |
SAS |
OTH |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/I | rs756868500  |
0.029 | None | N | 0.121 | 0.076 | None | gnomAD-2.1.1 | 2.01E-05 | None | None | None | None | N | None | 0 | 1.45113E-04 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| M/I | rs756868500 |
0.029 | None | N | 0.121 | 0.076 | None | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 1.31148E-04 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| M/I | rs756868500 |
0.029 | None | N | 0.121 | 0.076 | None | gnomAD-4.0.0 | 1.02505E-05 | None | None | None | None | N | None | 0 | 1.18725E-04 | None | 0 | 2.42648E-05 | None | 0 | 0 | 0 | 0 | 0 |
| M/T | rs2082519187 |
None | None | N | 0.137 | 0.139 | None | gnomAD-4.0.0 | 6.84255E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99501E-06 | 0 | 0 |
| M/V | None | None | None | N | 0.121 | 0.04 | None | gnomAD-4.0.0 | 1.59152E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43287E-05 | 0 |
Saturation Mutagenesis
SAV |
AlphaMissense (IC) |
AlphaMissense Class (IC) |
AlphaMissense (N2AB) |
AlphaMissense Class (N2AB) |
mCSM |
mCSM class |
PolyPhen-2 |
PolyPhen-2 Class |
Rhapsody |
Rhapsody Class |
Condel |
Condel Score |
Site annotation |
mCSM PPI |
Predicted PPI site |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.1773 | likely_benign | 0.1795 | benign | -0.488 | Destabilizing | None | N | 0.137 | neutral | None | None | None | None | N |
| M/C | 0.5804 | likely_pathogenic | 0.5829 | pathogenic | -0.514 | Destabilizing | 0.003 | N | 0.277 | neutral | None | None | None | None | N |
| M/D | 0.5241 | ambiguous | 0.523 | ambiguous | 0.536 | Stabilizing | None | N | 0.211 | neutral | None | None | None | None | N |
| M/E | 0.2211 | likely_benign | 0.2166 | benign | 0.496 | Stabilizing | None | N | 0.169 | neutral | None | None | None | None | N |
| M/F | 0.2325 | likely_benign | 0.233 | benign | -0.097 | Destabilizing | None | N | 0.166 | neutral | None | None | None | None | N |
| M/G | 0.3831 | ambiguous | 0.3815 | ambiguous | -0.69 | Destabilizing | None | N | 0.219 | neutral | None | None | None | None | N |
| M/H | 0.365 | ambiguous | 0.3688 | ambiguous | 0.094 | Stabilizing | 0.003 | N | 0.301 | neutral | None | None | None | None | N |
| M/I | 0.1054 | likely_benign | 0.1077 | benign | -0.046 | Destabilizing | None | N | 0.121 | neutral | N | 0.342463083 | None | None | N |
| M/K | 0.1194 | likely_benign | 0.119 | benign | 0.557 | Stabilizing | None | N | 0.137 | neutral | N | 0.38365418 | None | None | N |
| M/L | 0.0937 | likely_benign | 0.0914 | benign | -0.046 | Destabilizing | None | N | 0.114 | neutral | N | 0.320176141 | None | None | N |
| M/N | 0.308 | likely_benign | 0.3071 | benign | 0.679 | Stabilizing | None | N | 0.171 | neutral | None | None | None | None | N |
| M/P | 0.3359 | likely_benign | 0.3251 | benign | -0.163 | Destabilizing | None | N | 0.173 | neutral | None | None | None | None | N |
| M/Q | 0.1927 | likely_benign | 0.1909 | benign | 0.531 | Stabilizing | None | N | 0.121 | neutral | None | None | None | None | N |
| M/R | 0.1164 | likely_benign | 0.1109 | benign | 0.958 | Stabilizing | None | N | 0.176 | neutral | N | 0.386789248 | None | None | N |
| M/S | 0.2279 | likely_benign | 0.2306 | benign | 0.146 | Stabilizing | None | N | 0.137 | neutral | None | None | None | None | N |
| M/T | 0.0999 | likely_benign | 0.1029 | benign | 0.217 | Stabilizing | None | N | 0.137 | neutral | N | 0.371498742 | None | None | N |
| M/V | 0.0584 | likely_benign | 0.0588 | benign | -0.163 | Destabilizing | None | N | 0.121 | neutral | N | 0.320118495 | None | None | N |
| M/W | 0.4759 | ambiguous | 0.477 | ambiguous | -0.07 | Destabilizing | 0.051 | N | 0.343 | neutral | None | None | None | None | N |
| M/Y | 0.4311 | ambiguous | 0.4346 | ambiguous | 0.103 | Stabilizing | None | N | 0.219 | neutral | None | None | None | None | N |
Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.